The pharmacological effect of a medicine has been determined based on the change in clinical conditions (improvement or occurrence of a side effect).
The determination based on clinical conditions is possible only after a medicine is administered for a certain period of time.
Blood level monitoring has also been utilized in which the pharmacological effect of a medicine is evaluated indirectly by determining whether the blood level of a pharmaceutical agent derived from the medicine falls within the therapeutic range or the safe range that is obtained empirically. However, this method only takes effect on the precondition that there is a good correlation between the pharmacological effect and the blood level to some extent and that the therapeutic range or the safe range is clearly defined (“Hyojun-yakurigaku” (Standard Textbook of Pharmacology) 5th edition, edited by Akio Ebihara (1997) p.31), and moreover the method is merely indirect as the method for evaluating a pharmacological effect.
An object of the present invention is to evaluate the pharmacological effect of a medicine by providing a diagnostic reagent for determining accurately within a short time the degree of enhancement or inhibition of the function of a target (e.g., a bioenzyme or receptor) for the medicine upon the administration of the medicine.
In the screening of therapeutic compounds, a compound having as higher a therapeutic effect and as smaller side effect as possible is selected. Most of medicines exert the pharmacological effects by inhibiting or enhancing the function of their targets (e.g., bioenzymes or receptors). Accordingly, the pharmacological effect of a medicine can be evaluated by determining the degree of inhibition or enhancement of the function of a target for the medicine.
At present, the degree of inhibition or enhancement of the function of a target is evaluated in vitro. In recent years, an in vitro assay system called “HTS” (high throughput screening) which enables the processing of a large number of samples has been most common. This method uses a high density plate such as a 96-well, 384-well or 1536-well plate, utilizes techniques such as automation to great advantage, and can evaluate the pharmacological effect on a large number of samples up to hundreds of thousands at a high rate.
However, a result given in an in vitro evaluation does not always agree with a result given when a medicine is administered to an individual.
The only way to know the result of administering a medicine to an individual is to observe the change in clinical conditions (improvement or occurrence of a side effect) in the individual.
Accordingly, an object of the present invention is to provide a method and a reagent for screening pharmaceutical agents and/or prodrugs thereof for one or ones having high medicative efficacy and/or a small side effect by evaluating the degree of inhibition of a target in a whole body and in real time which is impracticable by any prior art technique.